Macrolides as immunomodulatory drugs in chronic lung diseases

Abstract

Macrolides have a variety of physiological activities other than antimicrobial effects. The non-antimicrobial properties of macrolides are grouped under the concept of immunomodulation. The spectrum of action of these antibiotics extends to regulation of leukocyte function and production of inflammatory mediators, control of mucus production, and modulation of respiratory epithelial defense. In addition, macrolides present anti-viral effects and are able to inhibit biofilm formation and reduce production of virulence factors from Pseudomonas aeruginosa. These properties of macrolides are mainly observed at low doses and for long-term treatments. There is a growing interest for the use of these drugs as immunomodulatory therapy for chronic lung diseases, mainly inflammatory diseases with acute exacerbation triggered by infections. The clinical benefits of macrolides to prevent acute exacerbation in chronic obstructive pulmonary disease and cystic fibrosis are well demonstrated. On the other side, there is no evidence that macrolides are efficient in asthma. Here, we review the physiological activities of macrolides including mechanisms by which they contribute to the clinical effects observed in chronic lung diseases. We also present the main clinical investigations regarding the use of macrolides in chronic obstructive pulmonary disease, cystic fibrosis, and asthma.